Synthesis and selected transformations of 3-oxido-1H-imidazole-4- carboxamides

Article abstract of DOI:10.1135/cccc2010012

An efficient synthesis of new N-alkyl- and N-aryl-3-oxido-1H-imidazole-4- carboxamides based on exploration of inexpensive, commercially available ethyl acetoacetate, paraformaldehyde and primary amines is described. Representative compounds were tested in selected transformations, such as 'sulfur-transfer reaction' leading to imidazole-2-thiones and isomerization to corresponding imidazol-2-ones. Strong intramolecular hydrogen bonding via the N-oxide function results in the reduced reactivity of 3-oxido-1H-imidazole-4-carboxamides in both reactions. Moreover, the palladium catalyzed C(2)-arylation of imidazole ring as well as azide-alkyne [3+2] cycloaddition using the N-propargyl substituted 4-carboxamide derived from an imidazole 3-oxide as a dipolarophile, were also studied.

Full text of DOI:10.1135/cccc2010012

3-Oxido-1H-imidazole-4-carboxamides
871
SYNTHESIS AND SELECTED TRANSFORMATIONS OF
3-OXIDO-1H-IMIDAZOLE-4-CARBOXAMIDES
1
2,
Grzegorz MLOSTOŃ and Marcin JASIŃSKI *
Department of Organic and Applied Chemistry, University of Łódź,
Tamka 12, PL-91-403 Łódź, Poland; e-mail: gmloston@uni.lodz.pl, mjasinski@uni.lodz.pl
1
2
Received January 29, 2010
Accepted April 13, 2010
Published online August 20, 2010
An efficient synthesis of new N-alkyl- and N-aryl-3-oxido-1H-imidazole-4-carboxamides
based on exploration of inexpensive, commercially available ethyl acetoacetate,
paraformaldehyde and primary amines is described. Representative compounds were tested
in selected transformations, such as ‘sulfur-transfer reaction’ leading to imidazole-2-thiones
and isomerization to corresponding imidazol-2-ones. Strong intramolecular hydrogen bond-
ing via the N-oxide function results in the reduced reactivity of 3-oxido-1H-imidazole-
4-carboxamides in both reactions. Moreover, the palladium catalyzed C(2)-arylation of imi-
dazole ring as well as azide-alkyne [3+2] cycloaddition using the N-propargyl substituted
4-carboxamide derived from an imidazole 3-oxide as a dipolarophile, were also studied.
Keywords: Imidazole N-oxides; Carboxamides; Hydrogen bond; 1,3-Dipolar cycloaddition;
Direct arylation.
1H-Imidazole N-oxides are recognized as easily accessible and useful build-
ing blocks in the modern organic chemistry1, including synthesis of biolog-
ically active compounds2. Special attention is focused on 2-unsubstituted
derivatives, which react with electron-deficient dipolarophiles analogously
to aldonitrons, yielding diversely functionalized imidazoles via initially
formed, unstable [3+2] cycloadducts3. However, in many cases, 2-unsubsti-
tuted imidazole N-oxides are described as reactive compounds and upon
heating, the UV irradiation or in the presence of an acylating agent,
smoothly undergo isomerization to yield the corresponding imidazol-
2-ones4. On the other hand, some derivatives, e.g. imidazole N-oxides bear-
ing alkylcarboxylic moiety attached to N(1) atom, are stable even in boiling
toluene5. In this case, the enhanced stability of the N-oxide form is ex-
plained by ‘the association between the N-oxide and COOH group’. How-
ever, extremely poor solubility of these products in common organic
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885
© 2010 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc2010012

872
Mlostoń, Jasiński:
solvents limits significantly their usefulness for standard synthetic method-
ologies.
Amides of type 2, derived from imidazole-4-carboxylic acid are known
and their remarkable stability was explained by the fact of an intra-
molecular hydrogen bonding between N→O function and the N-H amide
group located at C(4) (Fig. 1; R1 = alkyl or aryl, R2 = Me)6. More recently, we
described the synthesis and crystal-structure determination of N-cyclo-
propyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (derivative of
type 1), which proved that expectation (Fig. 1; R1 = R2 = Me, R3 = cProp)7.
In the present paper, a general method for the preparation of the
H-bonded 1-alkyl-3-oxido-1H-imidazole-4-carboxamides 1 supplemented by
some novel 1-aryl analogues 2 is described. In addition, some aspects re-
lated to the reactivities of N-oxides 1 and 2, relevant for their applications
in the synthesis of new imidazole derivatives, are studied.
FIG. 1
3-Oxido-1H-imidazole-4-carboxamides 1 and 2
RESULTS AND DISCUSSION
For the present study, easily accessible ethyl acetoacetate, paraformalde-
hyde, alkylamines, aniline or its p-substituted derivatives were applied as
starting materials for the synthesis of imidazole N-oxides 1 and 2, respec-
tively. The N-alkyl secondary amides 1 were prepared by aminolysis of cor-
responding ethyl esters 4 (Scheme 1). The initial experiment was carried
out using 4a and excess of methylamine (as ethanolic solution). In this case
the reaction solution was heated at 70 °C and after ca. 30 min. precipitation
of a colorless solid was observed. After 4 h heating reaction was complete
and product 1a was isolated in 77% yield. The same protocol was applied
for 4b and methylamine yielding 1b in 57% yield. The reactions of 4a with
cyclohexylamine and aminoethanol, were carried out analogously and
products 1c and 1f, respectively, were obtained. However, in the cases of
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

3-Oxido-1H-imidazole-4-carboxamides
873
allylamine and propargylamine, after 8 h heating, in both cases, conversion
was established below 10%, only. Therefore, both reactions were carried out
in neat using five- or six-fold excess of the corresponding alkylamine and
under that conditions, target products 1d and 1e were obtained in 81 and
59% yields, respectively. However, in the case of aniline, no expected prod-
uct was formed in the raction with 4a even after 6 h refluxing in EtOH.
Similarly, in the cases of sterically hindered alkylamines, such as 1-amino-
adamantane and (R)-(+)-phenylethylamine, no expected amides, derived
from imidazole N-oxides 1 were formed. Products 1a–1f were isolated in
satisfactory to good yields as high melting points, colorless solids, which
were fully characterized by spectroscopic and analytical data (Table I). In
TABLE I
N-Alkyl-3-oxido-1H-imidazole-4-carboxamides 1
1
R1
R2
Yield, %
M.p., °C
a
b
c
d
e
f
Me
n-Bu
Me
Me
Me
Me
Me
77
57
54
81
59
59
229–231
146–149
230–233
132–134
245–249
207–212
Me
cHex
allyl
propargyl
2-hydroxyethyl
SCHEME 1
Synthesis of N-alkyl- and N-cycloalkyl-3-oxido-1H-imidazole-4-carboxamides 1a–1f
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

874
Mlostoń, Jasiński:
1
the H NMR spectra, the expected diagnostic signals of C(2)-H were found
in the region 7.83–8.99 ppm. On the other hand, a broad signal of the
-CONH- was located at ca. 10.50 ppm, and in the case of 1a and 1c, the
3
coupling constants JH,H = 5.6 and 7.2 Hz, respectively, were observed.
Strong absorption bands located in the IR spectra of 1a–1f at ~1650 cm–1
proved the presence of the amide function.
Syntheses of N-oxides 4a (R1 = Me) and 4b (R1 = n-Bu) were performed
using ethyl α-hydroxyimino-β-oxobutyrate (3) and 1,3,5-trisubstituted
hexahydro-1,3,5-triazines (trimeric form of the corresponding N-alkyl form-
aldimines) in Et2O solutions at room temperature (Scheme 1). However, -
under these conditions, products 4 co-precipitated with 3 as colorless solids,
and after filtration, both compounds were separated chromatographically.
In the case of 4a, the reaction was repeated twice using recovered 3. Com-
bined fractions were recrystalized to give the expected products in fair
yields (60–70%). Alternatively, 4a and 4b were prepared in accordance with
literature protocol using glacial acetic acid as a solvent7,8. In this case, crude
products were converted in the corresponding hydrochlorides by passing
gaseous HCl through the reaction solutions and in the next step free N-ox-
ides 4 were isolated from MeOH–CHCl3 (1:3) solutions after neutralization
with solid sodium bicarbonate. In contrast to amides 1, esters 4 easily un-
dergo isomerization to yield corresponding imidazol-2-ones, even at low
temperature (0–5 °C). Therefore, they were used with no storage for the
aminolysis step. Starting compound 3 was obtained in multigram scale, fol-
lowing a literature protocol9.
The N-aryl secondary amides of type 2 were obtained from the corre-
sponding α-hydroxyimino-β-oxobutyramides 6 by condensation with
(N-methylidene)methylamine in boiling EtOH (Scheme 2, Table II)6. All
products were isolated as high-melting points, crystalline materials in good
yields.
TABLE II
N-Aryl-3-oxido-1H-imidazole-4-carboxamides 2
2
R1
Yield, %
M.p., °C
a
b
c
Ph
79
83
70
80
208–210
245–250
263–269
271–277
p-C6H5Br
p-C6H5F
d
p-C6H5BrNO2
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

3-Oxido-1H-imidazole-4-carboxamides
875
SCHEME 2
Synthesis of N-aryl-3-oxido-1H-imidazole-4-carboxamides 2a–2d
Compounds 6 were prepared from β-oxoamides 5 at 0–5 °C using aque-
ous solution of NaNO2 in glacial acetic acid. Amides 5 are accesible by two
different methods starting with ethyl acetoacetate and aniline or its p-sub-
stituted derivatives. In the case of 5a and 5b irradiation of the correspond-
ing mixture of substrates in commercial microwave oven at 600 Watt for
3–6 min turned out as a method of choice (94 and 78% yield, respec-
tively)10. However, attempted synthesis of 5c or 5d using this method
failed, and the expected products were isolated in very low yields (<5%),
only. Alternatively, required products were prepared by refluxing the corre-
sponding anilines with 50% excess of ethyl acetoacetate in dry xylenes.
Imidazole N-oxides of type 1 and 2, respectively were used for reactions
leading to urea- and thiourea-type imidazole derivatives (compounds 7 and
8, respectively) (Scheme 3). Since, neither compound 1 nor 2 isomerizes
upon heating in toluene, required imidazol-2-ones 7a and 7b, respectively,
were obtained by treatment of the corresponding N-oxides with excess of
Ac2O in dry CH2Cl2 at room temperature. Typically, 1,4,5-trisubstituted
imidazole N-oxides undergo complete conversion within ca. 2 h at room
temperature4a. However, in the cases of 1a and 2b, rearrangement of the
starting material under the same conditions was observed after 12 h (TLC
monitoring). Diminished reactivity of imidazole N-oxides 1 was also ob-
served in the ‘sulfur-transfer reaction’3a. The imidazole-2-thiones 8a–8b, ex-
pected in the reactions of 1a and 2a with 2,2,4,4-tetramethylcyclobutane-
1,3-dithione (9), were formed after 16 h, only. This is worth of noting, that
a typical conversion of an 2-unsubstituted imidazole N-oxide into the cor-
responding imidazole-2-thione was reported to take approximately 30
min3a.
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

876
Mlostoń, Jasiński:
SCHEME 3
Transformations of imidazole N-oxides 1a and 2a into corresponding imidazol-2-ones 7a–7b
and imidazole-2-thiones 8a–8b
Structures of imidazol-2-ones 7a–7b and imidazole-2-thiones 8a–8b were
1
proved by means of IR, NMR and HRMS data. For instance, the H NMR
spectrum of 7a (DMSO-d6) showed two NH signals registered as a singlet at
9.96 ppm and a broad doublet at 7.34 ppm, respectively. In the same spec-
trum, three signals assigned to Me groups were found at 2.32, 3.06 (2 s) and
3
1
2.69 ppm (d, JH,H = 4.6 Hz), respectively. On the other hand, the H NMR
spectrum of the same compound, recorded in CD3OD, revealed no signal
which could be attributed to the NH group and only three singlets of Me
groups were observed. Additionally, two broad absorptions at 1693 (vs) and
1645 (m) cm–1 in the IR spectrum, as well as two singlets of Cq atoms lo-
cated at 160.3 and 152.2 ppm in the 13C NMR spectrum, confirm the pres-
ence of two carbonyl groups.
Unexpectedly, in contrast to already reported 2-unsubstituted imidazole
N-oxides4a, analogous 1a and 2a do not react with cyanotrimethylsilane
(Me3SiCN, 3 equiv. in the presence of freshly dried molecular sieves 4Å)
even after 5 days at room temperature (CH3CN–CHCl3 solution).
In a very recent paper, excellent method for palladium catalyzed direct
arylation of α-unsubstituted azaaromatic N-oxides was reported2c. Follow-
ing this procedure, the mixture of equimolar amount of 1a and p-bromo-
fluorobenzene was heated in MeCN solution in the presence of Ph3P,
K2CO3 and Pd(OAc)2 (Scheme 4). The C(2)-cross-coupled imidazole N-oxide
10 was isolated as the only product in 70% yield.
Based on the general concept of [2+3] cycloaddition, the N-propargyl de-
rivative 1e is expected to act as a suitable dipolarophile in the azide-alkyne
‘click reaction’ catalyzed by Cu(I) salts (stepwise ‘Huisgen cycloaddition’)
(Scheme 5)11a. However, imidazole N-oxides are known to undergo
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

3-Oxido-1H-imidazole-4-carboxamides
877
SCHEME 4
Direct arylation of imidazole N-oxide 1a with 1-bromo-4-fluorobenzene
SCHEME 5
[3+2] Dipolar cycloaddition of N-propargyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide
(1e) with anisyl azide
smoothly deoxygenation in the presence of Cu(I) salts11b. Therefore, no
Cu(I) salts can be used to promote the ‘click reaction’ of the N-oxide 1e
with an organic azide. Thus, the EtOH solution containing 1e and a large
excess of 1-azido-4-methoxybenzene was refluxed for 80 h. The target
1
1,2,3-triazole 11 was isolated chromatographically in 67% yield. Its H NMR
spectrum reveales two singlets located at 8.66 and 8.60 ppm, respectively.
The elemental analysis confirmed the formula C16H18N6O3.
In summary, studies presented in this paper show that the condensations
of ethyl α-hydroxyimino-β-oxobutanoate (3) with corresponding 1,3,5-
hexahydrotriazines smoothly lead to 2-unsubstituted imidazole N-oxides 4,
bearing the ester group at C(4). Subsequent aminolysis of 4 with aliphatic
amines yield a new type of imidazole 4-carboxamides 1 with the preserved
N→O function. In the case of 4, attempted conversion into N-aryl substi-
tuted derivatives was in vain. Therefore, the corresponding anilides 2 were
obtained in a two-step procedure starting with acetylacetamides 5. In com-
parison with previously studied 4-aryl or 4-alkyl substituted analogues3,4
,
imidazole N-oxides 1 and 2 are less reactive towards acetic anhydride
(isomerization to imidazole-2-one) and 2,2,4,4-tetramethylcyclobutane-
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

878
Mlostoń, Jasiński:
1,3-dithione (sulfur transfer reaction). Moreover, they do not react with
cyanotrimethylsilane under typical conditions applied for the 2-cyanation
of imidazole N-oxides4a. Reduced reactivity of 1 and 2 is explained by the
presence of a strong intramolecular hydrogen bonding which diminishes
nucleophilicity (and basicity) of the N→O functional group.
2-Unsubstituted imidazole N-oxides of type 1 can be easily arylated at C(2)
using the ‘direct arylation’ procedure. In the case of the N-propargyl substi-
tuted derivative 1e, the corresponding 1,2,3-triazole 11 was obtained as the
product of a thermal [2+3] dipolar cycloadditon with p-methoxyphenyl
azide. In both cases the N→O function is preserved in the molecules of the
obtained products.
Presented results show that 4-carboxamide substituted imidazole N-
oxides 1 and 2 are versatile starting materials for synthesis of highly
functionalized imidazole derivatives and poliheterocyclic systems as well.
EXPERIMENTAL
General
Melting points were determined on a Melt-Temp. II apparatus (Aldrich) and are uncorrected.
The IR spectra were recorded on a NEXUS FT-IR spectrophotometer in KBr (ν, cm–1). The 1H
and 13C NMR spectra were measured on a Tesla BS567A (80 MHz), Varian Gemini 200 (200
and 50 MHz) or Bruker AC 400 (400 and 100 MHz) instruments using CDCl3, CD3OD or
DMSO-d6 as solvents. Chemical shifts (δ scale) are given in ppm (TMS = 0 ppm) and cou-
pling constants J in Hz. The multiplicity of the 13C signals was deduced from DEPT spectra.
The HRMS spectra were measured on a Finnigan MAT-95 instrument.
Starting Materials
Applied reagents such as ethyl acetoacetate, alkylamines, anilines, paraformaldehyde, diethyl
maleate, trimethylsilylcyanide and solvents are commercially available (Aldrich) and were
used as received. 1,3,5-Trialkylhexahydro-1,3,5-triazines were prepared from the correspond-
ing alkylamines and formaldehyde according to literature protocol12. 2,2,4,4-Tetramethyl-
cyclobutane-1,3-dithione13 and 1-azido-4-methoxybenzene14 were obtained following
known protocols. Ethyl α-hydroxyimino-β-oxobutanoate was obtained by nitrosation of
ethyl acetoacetate according to the published protocol9.
Synthesis of N-Alkyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamides 1a–1f
A mixture of imidazole N-oxide of type 4 (10 mmol) and corresponding amine (22 mmol) in
EtOH (10 ml) was heated at 70 °C (4–12 h, TLC monitoring: SiO2, AcOEt 1:4 MeOH). Then,
the solvent was removed under reduced pressure, crude product was washed with Et2O and
recrystallized.
Products 1d and 1e were prepared by heating 4a with excess (6 eq.) of corresponding
amine at 35 °C without solvent (neat) for 20 h.
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

3-Oxido-1H-imidazole-4-carboxamides
879
N-Methyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (1a). Yield 1.30 g (77%). Color-
less crystals, m.p. 229–231 °C (decomp.) (EtOH). IR (KBr): 3121 s, 1647 vs, 1599 vs, 1545 vs,
1457 m, 1409 m, 1373 m, 1324 m, 1285 m, 1162 m, 781 m, 757 m. 1H NMR (80 MHz,
CDCl3): 10.49 br. s, 1 H (NH); 7.83 s, 1 H (H-C(2)); 3.58 s, 3 H (NMe, imidazole); 2.94 d,
3 H, J = 5.6 (NHMe); 2.61 s, 3 H (Me). 13C NMR (50 MHz, CDCl3): 160.3 s (C=O); 131.0,
121.7 2s (C(4), C(5)); 125.9 d (C(2)); 31.9, 24.8, 9.1 3q (3 Me). EI-HRMS: 169.0857 (M+,
C7H11N3O2+; calculated 169.0851).
N-Methyl-1-butyl-5-methyl-3-oxido-1H-imidazole-4-carboxamide (1b). Yield 1.20 g (57%). Col-
orless crystals, m.p. 146–149 °C (CH2Cl2–Et2O). IR (KBr): 3093 m, 3018 m, 2958 m, 2933 m,
1653 vs, 1598 vs, 1564 m, 1469 m, 1419 m, 1370 m, 1287 m, 759 m. 1H NMR (200 MHz,
CDCl3): 10.13 br. s, 1 H (NH); 7.84 s, 1 H (H-C(2)); 3.68 t, 2 H, J = 7.3 (n-Bu); 2.74 d, 3 H,
J = 5.0 (NHMe); 2.41 s, 3 H (Me); 1.60–1.45 m, 2 H (n-Bu); 1.21–1.10 m, 2 H (n-Bu); 0.75 t,
3 H, J = 7.2 (n-Bu). 13C NMR (50 MHz, CDCl3): 160.2 s (C=O); 130.2, 122.0 2s (2 arom. C);
125.2 d (C(2)-H); 45.4, 25.1, 19.5 3t (3 -CH2-, n-Bu); 32.0, 13.4, 9.5 3q (3 Me). EI-HRMS:
211.1339 (M+, C10H17N3O2+; calculated 211.1321).
N-Cyclohexyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (1c). Yield 1.28 g (54%). Col-
orless crystals, m.p. 230–233 °C (decomp.) (EtOH). IR (KBr): 3088 m, 3027 m, 2931 vs,
2858 m, 1655 vs, 1605 vs, 1560 m, 1450 m, 1416 m, 1378 m, 1290 m, 758 m, 631 m,
602 m. 1H NMR (400 MHz, CDCl3): 10.56 br. d, 1 H, J = 7.2 (NH); 7.85 s, 1 H (H-C(2));
4.01–3.92 m, 1 H (cHex); 3.60 s, 3 H (NMe); 2.62 s, 3 H (Me); 1.95–1.92, 1.76–1.72 2m, 4 H
(cHex); 1.60–1.27 m, 6 H (cHex). 13C NMR (100 MHz, CDCl3): 158.7 s (C=O); 130.7, 122.4 2s
(2 arom. C); 125.2 d (C(2)); 47.2 d (CH, cHex); 32.8, 25.6, 24.6 3t (5 CH2, cHex); 32.1 q
(NMe); 9.5 q (Me). EI-HRMS: 237.1471 (M+, C12H19N3O2+; calculated 237.1477).
N-Allyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (1d). Yield 1.60 g (81%). Colorless
solid, m.p. 132–134 °C (acetone). IR (KBr): 3114 m, 3089 m, 2988 m, 1657 vs, 1641 s,
1602 vs, 1557 s, 1451 m, 1439 m, 1411 m, 1368 m, 1290 m, 754 m, 629 m, 606 m. 1H NMR
(80 MHz, CDCl3): 10.82 br. s, 1 H (NH); 7.78 s, 1 H (H-C(2)); 6.18–5.72 m, 1 H
(-CH2-CH=CH2); 5.40–5.04 m, 2 H (-CH2-CH=CH2); 4.14–3.96 m, 2 H (-CH2-CH=CH2);
3.58 s, 3 H (NMe); 2.62 s, 3 H (Me). 13C NMR (50 MHz, CDCl3): 159.4 s (C=O); 134.1 d
(-CH2-CH=CH2); 131.3, 122.0 2s (2 arom. C); 126.2 d (C(2)); 115.8 t (=CH2); 40.7 t (-CH2-);
32.2 q (NMe); 9.4 q (Me). EI-HRMS: 195.1019 (M+, C9H13N3O2+; calculated 195.1008).
N-Propargyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (1e). Yield 1.14 g (59%). Col-
orless crystals, m.p. 245–249 °C (decomp.) (EtOH). IR (KBr): 3214 s, 3112 m, 3042 m,
1652 vs, 1602 s, 1544 s, 1453 m, 1415 m, 1376 m, 1349 m, 1287 m, 739 s, 625 m, 603 m.
1H NMR (200 MHz, CDCl3): 9.72 br. s, 1 H (NH); 8.99 s, 1 H (H-C(2)); 4.20 dd, 2 H, J = 5.4,
2.5 (-CH2-); 3.75 s, 3 H (NMe); 2.63 s, 3 H (Me); 2.25 t, 1 H, J = 2.5 (-C≡CH). 13C NMR
(50 MHz, CDCl3): 158.3 s (C=O); 132.6, 121.3 2s (2 arom. C); 128.2 d (C(2)); 79.3 s (-C≡CH);
71.3 d (-C≡CH); 32.8 q (NMe); 28.3 t (-CH2-); 9.5 q (Me). EI-HRMS: 193.0862 (M+,
C9H11N3O2+; calculated 193.0851).
N-(2-Hydroxyethyl)-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (1f). Yield 1.17 g (59%).
Colorless crystals, m.p. 207–212 °C (decomp.) (EtOH). IR (KBr): 3163 vs (br.), 3115 s, 1652
vs, 1595 s, 1538 s, 1450 m, 1281 m, 1061 m, 756 m, 623 m, 607 m. 1H NMR (200 MHz,
DMSO-d6): 10.96 br. t, 1 H, J = 5.2 (NH); 8.41 s, 1 H (H-C(2)); 4.83 t, 1 H, J = 5.0 (OH);
3.56 s, 3 H (NMe); 3.48 t, 2 H, J = 5.1 (-CH2-); 3.33 t, 2 H, J = 5.6 (-CH2-); 2.50 s, 3 H (Me).
13C NMR (50 MHz, DMSO-d6): 159.5 s (C=O); 130.2, 120.4 2s (2 arom. C); 126.0 d (C(2));
59.9, 40.3 2t (2 -CH2-); 31.7 q (NMe); 9.0 q (Me). EI-HRMS: 199.0956 (M+, C8H13N3O3+; cal-
culated 199.0957).
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

880
Mlostoń, Jasiński:
Synthesis of N-Aryl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamides (2)
A mixture of 1,3,5-trimethylhexahydro-1,3,5-triazine (0.55 g, 4.3 mmol) and corresponding
α-hydroxyimino-β-oxobutyramide 6 (10 mmol) in ethanol (15 ml) was refluxed for 3 h. The
solvent was removed under vacuum, the crude product was washed with Et2O and
recrystallized.
N-Phenyl-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide6 (2a). Yield 1.82 g (79%). Color-
less crystals, m.p. 208–210 °C (EtOH–H2O). IR (KBr): 3363 m, 3012 m, 1671 vs, 1612 vs,
1597 vs, 1559 vs, 1504 m, 1491 s, 1445 s, 1411 m, 1376 m, 1313 s, 1273 m, 1150 m, 762 s.
1H NMR (80 MHz, CDCl3): 12.95 br. s, 1 H (NH); 7.86 s, 1 H (H-C(2)); 7.77–7.59 m (2 arom. H);
7.46–6.94 m (3 arom. H); 3.72 s, 3 H (NMe); 2.63 s, 3 H (Me).
N-(p-Bromophenyl)-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (2b). Yield 2.57 g (83%).
Colorless crystals, m.p. 245–250 °C (decomp.) (EtOH). IR (KBr): 3145 m, 1655 s, 1610 vs,
1592 s, 1555 vs, 1488 s, 1448 m, 1398 m, 1369 m, 1307 s, 1267 m, 1267 m, 1149 m,
1070 m, 824 m, 803 m, 768 m, 606 m. 1H NMR (400 MHz, CDCl3): 12.73 br. s, 1 H (NH);
8.07 s, 1 H (H-C(2)); 7.53 d, J = 8.8 (2 arom. H); 7.41 d, J = 8.8 (2 arom. H); 3.62 s, 3 H
(NMe); 2.60 s, 3 H (Me). 13C NMR (100 MHz, CDCl3): 157.9 s (C=O); 137.2, 133.3, 121.6,
117.4 4s (4 arom. C); 132.4, 122.5 2d (4 arom. CH); 127.2 d (C(2), imidazole); 32.8 q (NMe);
9.9 q (Me). EI-HRMS: 309.0109 (M+, C12H12BrN3O2+; calculated 309.0113).
N-(p-Fluorophenyl)-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (2c). Yield 1.74 g (70%).
Colorless crystals, m.p. 263–269 °C (EtOH). IR (KBr): 3007 m, 3100–2400 m (br.), 1670 s,
1621 vs, 1578 s, 1507 vs, 1449 m, 1411 m, 1377 m, 1316 m, 1216 m, 837 m. 1H NMR
(80 MHz, CDCl3): 12.96 br. s, 1 H (NH); 7.85 s, 1 H (H-C(2)); 7.76–7.59 m (2 arom. H);
7.13–6.91 m (2 arom. H); 3.61 s, 3 H (NMe); 2.66 s, 3 H (Me). 13C NMR (50 MHz, CDCl3):
1
4
159.2 d, JC-F = 241.8 (1 arom. C); 157.3 s (C=O); 134.0 d, JC-F = 2.8 (1 arom. C); 131.8,
3
121.8 2s (2 arom. C, imidazole); 125.7 d (C(2), imidazole); 122.0 d, JC-F = 7.8 (2 arom. CH);
2
115.5 d, JC-F = 22.5 (2 arom. CH); 32.2 q (NMe); 9.5 q (Me). EI-HRMS: 249.0924 (M+,
C
12H12FN3O2+; calculated 249.0914).
N-(4-Nitrophenyl)-1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (2d). Yield 2.21 g (80%).
Orange solid, m.p. 271–277 °C (decomp.) (EtOH). IR (KBr): 1674 m, 1622 m, 1577 vs,
1500 s, 1448 m, 1405 m, 1375 m, 1327 vs, 1302 s, 1282 s, 1151 m, 1107 m, 853 m, 801 m,
605 m. 1H NMR (200 MHz, DMSO-d6): 14.27 br. s, 1 H (NH); 8.61 s, 1 H (H-C(2)); 8.23 d, J =
9.2 (2 arom. H); 7.86 d, J = 9.2 (2 arom. H); 3.60 s, 3 H (NMe); 2.55 s, 3 H (Me). 13C NMR
(50 MHz, CDCl3): 158.0 s (C=O); 144.2, 142.7, 133.1, 118.9 4s (4 arom. C); 125.2, 119.4 2d
(4 arom. CH); 127.5 d (C(2), imidazole); 32.0 q (NMe); 9.2 q (Me). EI-HRMS: 276.0858 (M+,
C
12H12N4O4+; calculated 276.0858).
Sythesis of Ethyl 3-oxido-1H-imidazole-4-carboxylates (4)
To the solution of (α-hydroxyimino)ketone 3 (10 mmol) in Et2O (5 ml), a solution of corre-
sponding 1,3,5-trialkylhexahydro-1,3,5-triazine (0.45 mmol) in Et2O (2 ml) was added at
0 °C; when the addition was complete, the cooling bath was removed. The mixture was
magnetically stirred for 24 h, the colorless precipitate was filtered and flash chromatog-
raphed (SiO2, Me2CO and then AcOEt–MeOH (1:1) mixture) to give the starting 3 and the
crude product 4. The reaction and purification were repeated twice using recovered 3. Com-
bined fractions of crude products 4 were recrystallized from the appropriate solvents. Alter-
natively, the synthesis of 4a and 4b was repeated using glacial acetic acid as solvent to give
target products in 82 and 61% yield, respectively7,8
.
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

3-Oxido-1H-imidazole-4-carboxamides
881
Ethyl 1,5-dimethyl-3-oxido-1H-imidazole-4-carboxylate7 (4a). Yield 1.23 g (67%). Colorless
crystals, m.p. 76–78 °C (CH2Cl2–Et2O). 1H NMR (80 MHz, CDCl3): 8.13 s, 1 H (H-C(2));
4.34 q, 2 H, J = 7.0 (OEt); 3.59 s, 3 H (NMe); 2.47 s, 3 H (Me); 1.39 t, 3 H, J = 7.0 (OEt).
Ethyl 1-butyl-5-methyl-3-oxido-1H-imidazole-4-carboxylate (4b). Yield 1.31 g (58%). Colorless
oil. IR (KBr): 2980–2850 m (br.), 1697 vs, 1610 m, 1453 m, 1320 m, 1183 m, 1076 m,
755 m. 1H NMR (200 MHz, CDCl3): 8.08 s, 1 H (H-C(2)); 4.32 q, 2 H, J = 7.1 (OEt); 3.81 t,
2 H, J = 7.1 (Bu); 2.40 s, 3 H (Me); 1.78–1.26 m, 4 H (Bu); 1.31 t, 3 H, J = 7.1 (OEt); 0.87 t,
3 H, J = 7.1 (Bu). 13C NMR (50 MHz, CDCl3): 159.0 s (C=O); 131.7, 121.6 2s (2 arom. C);
126.8 d (C(2)); 60.8 t (OEt); 45.6, 31.8, 19.3 3t (3 CH2, Bu); 14.0 q (OEt); 13.2 q (CH3, Bu);
9.9 q (Me). EI-HRMS: 226.1322 (M+, C11H18N2O3+; calculated 226.1317).
Synthesis of Acetoacetanilides (5)
Method A (MW induced acetoacetylation of amines): A mixture of ethyl acetoacetate
(3 mmol) and corresponding amine (1 mmol) was placed in an Ehrlenmeyer flask equiped
with conical adapter containing silica gel. The reaction mixture was irradiated at 600 W in
a commercial microwave oven for required time. The resulting residue was washed with pe-
troleum ether and filtered, and the crude product was recrystallized from EtOH.
3-Oxo-N-phenylbutyramide10 (5a): Time 6 min. Yield 166 mg (94%). Colorless crystals, m.p.
79–81 °C (EtOH). IR (KBr): 3288 m, 3254 m, 1725 vs, 1713 vs, 1662 vs, 1600 s, 1541 s,
1498 s, 1446 s, 1409 s, 1362 m, 1341 m, 1314 m, 1167 m, 755 s, 691 s. 1H NMR (80 MHz,
CDCl3): 9.05 br. s, 1 H (NH); 7.64–7.07 m (5 arom. H); 3.55 s, 2 H (CH2); 2.30 s, 3 H (CH3).
N-(4-Bromophenyl)-3-oxobutyramide10 (5b): Time 3 min. Yield 189 mg (78%). Colorless crys-
tals, m.p. 142–143 °C (EtOH). IR (KBr): 3288 m, 3250 m, 1716 vs, 1659 vs, 1605 s, 1552 s,
1490 s, 1416 m, 1395 m, 1361 m, 1341 m, 1312 m, 1161 m, 1075 m, 832 s, 816 m. 1H NMR
(80 MHz, CDCl3): 9.21 br. s, 1 H (NH); 7.43 s (4 arom. H); 3.57 s, 2 H (CH2); 2.32 s, 3 H
(CH3).
Method B (Thermal condensation): A mixture of ethyl acetoacetate (15 mmol) and corre-
sponding aniline (10 mmol) in dry xylene (25 ml) was placed in a round-bottomed flask,
equipped with a Dean–Stark apparatus and heated under reflux for 8 h. The crude mixture
was flash chromatographed (SiO2, petroleum ether, then AcOEt), the solvents were removed,
the oily residue was treated with Et2O, cooled and filtered. The obtained crude solid was pu-
rified by recrystallization from appropriate solvent to give analytically pure 5.
N-(4-Flurophenyl)-3-oxobutyramide (5c). Yield 0.21 g (11%). Colorless solid, m.p. 94–96 °C
(EtOH). IR (KBr): 3258 m, 3069 m, 1720 s, 1666 vs, 1621 m, 1569 m, 1553 m, 1511 vs,
1414 s, 1215 m, 1167 s, 838 s. 1H NMR (200 MHz, CDCl3): 9.25 br. s, 1 H (NH); 7.49–7.43 m
(2 arom. H); 7.00–6.92 m (2 arom. H); 3.53 s, 2 H (CH2); 2.26 s, 3 H (CH3). 13C NMR
1
(50 MHz, CDCl3): 205.0 s (C=O); 164.0 s (CONH); 159.5 d, JC-F = 242.5 (1 arom. C);
4
3
2
133.5 d, JC-F = 2.8 (1 arom. C); 122.0 d, JC-F = 7.9 (2 arom. CH); 115.5 d, JC-F = 22.3
(2 arom. CH); 49.8 t (CH2); 30.9 q (CH3). EI-HRMS: 195.0713 (M+, C10H10FNO2+; calculated
195.0696).
N-(4-Nitrophenyl)-3-oxobutyramide15 (5d). Yield 1.06 g (48%). Light yellow needles, m.p.
151–152 °C (decomp.) (EtOH). IR (KBr): 3303 m, 3271 m, 1717 s, 1668 vs, 1617 m, 1596 m,
1570 vs, 1514 vs, 1419 m, 1411 m, 1336 vs, 1159 m, 1115 m, 857 m, 749 m. 1H NMR
(200 MHz, CDCl3): 9.68 br. s, 1 H (NH); 8.20 d, J = 8.8 (2 arom. H); 7.73 d, J = 8.3 (2 arom. H);
3.64 s, 2 H (CH2); 2.34 s, 3 H (CH3).
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

882
Mlostoń, Jasiński:
Synthesis of 2-Hydroxyimino-3-oxobutyramides (6)
To the saturated solution of amide 5 (10 mmol) in glacial acetic acid (ca. 5–10 ml) cooled to
5 °C, a solution of NaNO2 (1.0 g, 14 mmol) in H2O (3 ml) was added dropwise. Then, cool-
ing bath was removed and the resulting mixture was stirred at room temperature for 1 h, di-
luted with H2O (ca. 100 ml) and cooled. The obtained portions of precipitate were collected,
washed with H2O, dried and recrystallized.
2-Hydroxyimino-3-oxo-N-phenylbutyramide16 (6a). Yield 1.83 g (89%). Light yellow needles,
m.p. 98–100 °C (CHCl3–petroleum ether). IR (KBr): 3250–3000 m (br.), 1680 vs, 1644 m,
1604 s, 1566 s, 1537 vs, 1496 s, 1407 s, 1361 s, 1292 s, 1104 m, 1036 s, 898 m, 769 s.
1H NMR (80 MHz, CDCl3): 17.00 s, 1 H (NOH); 10.48 br. s, 1 H (NH); 7.70–7.18 m (5 arom. H);
2.48 s, 3 H (CH3).
N-(4-Bromophenyl)-2-hydroxyimino-3-oxobutyramide17 (6b). Yield 1.85 g (65%). Colorless
solid, m.p. 204–209 °C (decomp.) (EtOH–benzine). IR (KBr): 3350–3000 m (br.), 3334 vs,
1683 vs, 1659 vs, 1626 m, 1606 s, 1549 vs, 1489 s, 1420 m, 1400 s, 1073 m, 1000 s, 818 m.
1H NMR (80 MHz, CD3OD): 7.63–7.35 m (4 arom. H); 2.41 s, 3 H (CH3).
N-(4-Flurophenyl)-2-hydroxyimino-3-oxobutyramide (6c). Yield 0.76 g (34%). Colorless nee-
dles, m.p. 121–123 °C (petroleum). IR (KBr): 3330 s, 3250–2950 m (br.), 1686 vs, 1656 vs,
1621 s, 1565 s, 1509 s, 1424 m, 1412 s, 1366 m, 1296 m, 1230 m, 1080 m, 1001 vs, 825 s.
1H NMR (200 MHz, CDCl3): 16.94 s, 1 H (NOH); 10.97 br. s, 1 H (NH); 7.60–7.53 m (2 arom. H);
7.07–7.03 m (2 arom. H); 2.57 s, 3 H (CH3). 13C NMR (50 MHz, CDCl3): 200.3 s (C=O);
1
4
161.3 s (CONH); 160.5 d, JC-F = 245.6 (1 arom. C); 143.4 s (C=N); 131.4 d, JC-F = 2.8
3
2
(1 arom. C); 123.1 d, JC-F = 7.9 (2 arom. CH); 116.1 d, JC-F = 22.6 (2 arom. CH); 26.2 q
(CH3). EI-HRMS: 224.0601 (M+, C10H9FN2O3+; calculated 224.0597).
2-Hydroxyimino-N-(4-nitrophenyl)-3-oxobutyramide18 (6d). Yield 1.48 g (59%). Light yellow
crystals, m.p. 179–182 °C (H2O). 1H NMR (80 MHz, CDCl3): 16.72 br. s, 1 H (NOH);
11.37 br. s, 1 H (NH); 8.12 m (2 arom. H); 7.83 m (2 arom. H); 2.59 s, 3 H (CH3).
Synthesis of Imidazol-2-ones (7)
To the suspension of 1a (0.17 g, 1.0 mmol) or 2a (0.23 g, 1.0 mmol) in CH2Cl2 (5 ml),
cooled with an external ice-water bath, a solution of freshly distilled Ac2O (1.8 g, 17.6 mmol)
in CH2Cl2 (6 ml) was added dropwise. Then, the reaction solution was allowed to warm to
room temperature and subsequently stirred for 12 h. The excess of MeOH was added
carefully while stirring for another 15 min, and the solvents were removed in vacuum (1–5
Torr). Crude product 7 was recrystallized to give a colorless solid.
N-Methyl-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide (7a). Yield 82 mg
(48%). Colorless crystals, m.p. 272–273 °C (decomp.) (EtOH). IR (KBr): 3370 s, 1693 vs,
1645 s, 1598 s, 1557 s, 1431 m, 1372 m. 1H NMR (200 MHz, DMSO-d6): 9.96 br. s, 1 H (NH);
7.34 br. d, 1 H (NH); 3.06 s, 3 H (NMe, imidazole); 2.69 d, 3 H, J = 4.6 Hz (NHMe); 2.32 s,
3 H (Me). 13C NMR (50 MHz, DMSO-d6): 160.3, 152.2 2s (2 C=O); 127.1, 111.0 2s (2 arom. C);
26.6, 25.6, 9.6 3q (3 Me). EI-HRMS: 169.0847 (M+, C7H11N3O2+; calculated 169.0851).
N-Phenyl-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide (7b). Yield 168 mg
(73%). Colorless solid, m.p. 299–304 °C (decomp.) (MeOH). IR (KBr): 1695 vs, 1663 vs,
1629 vs, 1601 m, 1550 s, 1499 m, 1486 m, 1435 m, 1353 s, 1239 m, 749 m. 1H NMR
(200 MHz, DMSO-d6): 10.34, 9.22 br. 2s, 2 H (2 NH); 7.64–7.61 m (2 arom. H); 7.36–7.28 m
(2 arom. H); 7.09–7.02 m (1 arom. H); 3.11 s, 3 H (NMe); 2.38 s, 3 H (Me). 13C NMR
(50 MHz, DMSO-d6): 158.0, 152.1 2s (2 C=O); 139.0, 129.5, 110.7 3s (3 arom. C); 128.9,
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

3-Oxido-1H-imidazole-4-carboxamides
883
+
123.5, 119.8 3d (5 arom. CH); 26.7, 9.8 2q (2 Me). EI-HRMS: 231.1013 (M+, C12H13N3O2
calculated 231.1008).
;
Synthesis of Imidazole-2-thiones (8)
To the magnetically stirred solution of 1a (0.26 g, 1.5 mmol) or 2a (0.35 g, 1.5 mmol) in
CH2Cl2 (10 ml), a solution of 2,2,4,4-tetramethylcyclobutane-1,3-dithione (9; 0.19 g, 1.1 mmol)
in dichloromethane (2 ml) was added at 0 °C. When the addition was complete, the ice bath
was removed and the stirring was continued overnight. Next day, the solvent was evaporated to
dryness, the crude product was washed with ether twice and purified by recrystallization from
EtOH.
N-Methyl-1,5-dimethyl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxamide (8a). Yield 0.26 g
(91%). Colorless crystals, m.p. 263–264 °C (decomp.). IR (KBr): 3300–3050 vs (br.), 1640 vs,
1606 s, 1556 s, 1489 s, 1447 m, 1422 m, 1405 m, 1383 m, 1371 s, 1273 m. 1H NMR (200 MHz,
DMSO-d6): 12.21 br. s, 1 H (NH); 7.71 br. d, 1 H (NH); 3.43 s, 3 H (NMe, imidazole); 2.72 d,
3 H, J = 4.6 Hz (NHMe); 2.42 s, 3 H (Me). 13C NMR (50 MHz, DMSO-d6): 161.4, 159.0 2s
(C=S, C=O); 132.3, 117.7 2s (2 arom. C); 30.7, 25.7, 10.1 3q (3 Me). EI-HRMS: 185.0627 (M+,
C7H11N3OS+; calculated 185.0623).
N-Phenyl-1,5-dimethyl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxamide (8b). Yield 0.30 g
(80%). Colorless crystals, m.p. 284–288 °C (decomp.). IR (KBr): 3250–2900 vs (br.), 1667 vs,
1600 s, 1544 s, 1498 s, 1444 s, 1366 s, 1242 m, 760 m. 1H NMR (200 MHz, DMSO-d6):
12.48 br. s, 1 H (NH); 9.58 br. s, 1 H (NH); 7.66–7.64 m (2 arom. H); 7.35–7.33 m
(2 arom. H); 7.10–7.08 m (1 arom. H); 3.47 s, 3 H (NMe); 2.49 s, 3 H (Me). 13C NMR
(50 MHz, DMSO-d6): 161.7, 156.6 2s (C=S, C=O); 138.7, 134.2, 117.4 3s (3 arom. C); 128.9,
123.9, 119.8 3d (5 arom. CH); 30.8, 10.3 2q (2 Me). EI-HRMS: 247.0780 (M+, C12H13N3OS+;
calculated 247.0779).
Synthesis of N-Methyl-2-(4-fluorophenyl)-1,5-dimethyl-3-oxido-1H-imidazole-
4-carboxamide (10)
A solution containing 1a (0.80 g, 4.7 mmol), (p-bromo)fluorobenzene (0.75 g, 4.3 mmol),
Pd(OAc)2 (50 mg, 5 mole %), PPh3 (170 mg, 15 mole %) and anhydrous K2CO3 (1.2 g,
8.6 mmol) in dry MeCN (10 ml) was heated at 75 °C under argon atmosphere for 6 h. The
reaction solution was diluted with the CHCl3–MeOH (8:2) mixture (50 ml), filtered through
the celite plug, and the filtrate was evaporated to dryness. The obtained solid was purified
by column chromatography (SiO2, CHCl3, then CHCl3–MeOH (95:5), RF 0.43) to give 10
(0.87 g, 70%) as a colorless solid, m.p. 227–228 °C (decomp.) (CHCl3–Et2O). IR (KBr):
3100–2850 m (br.), 1659 vs, 1604 s, 1568 m, 1563 m, 1471 m, 1408 m, 1378 m, 1293 m,
1230 m, 1164 m, 852 w, 837 w, 658 w, 605 w, 580 w. 1H NMR (400 MHz, CDCl3): 10.91 br.
s, 1 H (NH); 7.87 br. s (2 arom. H); 7.42 br. s (2 arom. H); 3.53 s, 3 H (NMe); 2.82 s, 3 H
1
(NHMe); 2.57 s, 3 H (Me). 13C NMR (100 MHz, DMSO-d6): 162.6 d, JC-F = 247 (1 arom. C);
3
160.0 s (C=O); 132.6 d, JC-F = 9 (2 arom. CH); 130.0, 128.4, 119.8 3s (3 arom. C); 119.9 d,
3
4JC-F = 3 (1 arom. C); 115.6 d, JC-F = 22 (2 arom. CH); 31.8, 24.5, 9.4 3q (3 Me). EI-HRMS:
263.1064 (M+, C13H14FN3O2+; calculated 263.1070).
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

884
Mlostoń, Jasiński:
Synthesis of N-[1-(4-Methoxyphenyl)-1H-(1,2,3-triazol-4-ylmethyl)]-
1,5-dimethyl-3-oxido-1H-imidazole-4-carboxamide (11)
A solution of 1e (0.16 g, 0.8 mmol) and 1-azido-4-methoxybenzene·2 MeOH (1.06 g,
5.0 mmol) (added in two equal portions – the second one after ca. 40 h) in ethanol (30 ml)
was refluxed for 80 h. The solvent was removed and the obtaned material was filtered
through the silica gel plug (Me2CO, then MeOH). The crude product obtained thereby was
purified by column chromatography (SiO2, MeOH). Yield 0.19 g (67%). Colorless crystals,
m.p. 206–210 °C (decomp.) (CH2Cl2–acetone). IR (KBr): 3110–2840 s (br.), 1652 s, 1602 s,
1560 m, 1547 m, 1518 s, 1440 m, 1289 m, 1248 m, 1226 m, 1189 m, 1038 m, 839 m,
620 m, 602 m. 1H NMR (400 MHz, DMSO-d6): 10.79 br s, 1 H (NH); 8.66, 8.60 2s, 2 H (imi-
dazole, triazole); 7.79, 7.12 2d, 4 H, J = 8.8 (Ph); 4.61 d, 2 H, J = 5.6 (-CH2-); 3.82, 3.60 2s,
6 H (OMe, NMe); 2.52 s, 3 H (Me). 13C NMR (100 MHz, DMSO-d6): 157.7 s (C=O); 159.2,
145.7, 131.9, 130.6, 127.2 5s (5 arom. C); 122.2, 121.7, 120.7, 114.7 4d (6 arom. CH); 55.6 q
(OMe); 34.4 t (-CH2-); 32.5 q (NMe); 9.5 q (Me). ESI-MS: 707 (100, [M + M + Na]+), 365 (37,
[M + Na]+), 343 (26, [M + H]+). For C16H18N6O3 (342.14) calculated: 56.12% C, 5.30% H,
24.56% N; found: 55.89% C, 5.07% H, 24.76% N.
The authors thanks the Rector of the University of Łódź (University Grant No. 505/0712) and
the Polish Ministry for Science and Higher Education for generous support. Help by Dr. E. Röcker
(JLU Giessen) in registration of the HRMS spectra is also acknowledged.
REFERENCES
1. a) Bartnik R., Hahn W., Mlostoń G.: Roczniki Chem. 1977, 51, 49; b) Ferguson I. J.,
Schofield K.: J. Chem. Soc., Perkin Trans. 1 1975, 275; c) Alcázar J., Begtrup M., de la
Hoz A.: J. Chem. Soc., Perkin Trans. 1 1995, 2467; d) Cerecetto H., Gerpe A., Gonzáles M.,
Fernández Sainz Y., Piro O. E., Castellano E. E.: Synthesis 2004, 2678.
2. a) Laufer S., Wagner G., Kotschenreuther D.: Angew. Chem., Int. Ed. 2002, 41, 2290;
b) Aguirre G., Boiani M., Cerecetto H., Gerpe A., González M., Sainz Y. F., Denicola A.,
de Ocáriz C. O., Nogal J. J., Montero D., Escario J. A.: Arch. Pharm. Pharm. Med. Chem.
2004, 337, 259; c) Campeau L.-C., Stuart D. R., Leclerc J.-P., Bertrand-Laperle M.,
Villemure E., Sun H.-Y., Lasserre S., Guimond N., Lecavallier M., Fagnou K.: J. Am. Chem.
Soc. 2009, 131, 3291; d) Mlostoń G., Jasiński M., Heimgartner H.: J. Heterocycl. Chem.
2010, 47, in press.
3. a) Mlostoń G., Gendek T., Heimgartner H.: Helv. Chim. Acta 1998, 81, 1585; b) Mlostoń G.,
Gendek T., Heimgartner H.: Tetrahedron 2000, 56, 5405; c) Mlostoń G., Jasiński M.,
Linden A., Heimgartner H.: Helv. Chim. Acta 2006, 89, 1304.
4. a) Mlostoń G., Celeda M., Prakash G. K. S., Olah G. A., Heimgartner H.: Helv. Chim. Acta
2000, 83, 728; b) Jasiński M.: Ph.D. Thesis. University of Łódź, Łódź 2008.
5. Lettau H.: Z. Chem. 1970, 10, 462.
6. Hossbach R., Lettau H., Nuhn P., Schneider R., Stenger P., Stiebitz B.: Pharmazie 1991,
46, 412.
7. Jasiński M., Mlostoń G., Linden A., Heimgartner H.: Helv. Chim. Acta 2008, 91, 1916.
8. Mucha P., Mlostoń G., Jasiński M., Linden A., Heimgartner H.: Tetrahedron: Asymmetry
2008, 19, 1600.
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885

3-Oxido-1H-imidazole-4-carboxamides
885
9. Corrêa I. R., Jr., Moran P. J. S.: Tetrahedron 1999, 55, 14221.
10. Suri O. P., Satti N. K., Suri K. A.: Synth. Commun. 2000, 30, 3709.
11. a) Rostovtsev V. V., Green L. G., Fokin V. V., Sharpless K. B.: Angew. Chem., Int. Ed.
2002, 41, 2596; b) Singh S. K., Reddy M. S., Mangle M., Ganesh K. R.: Tetrahedron 2007,
63, 126.
12. Kahovec L.: Z. Phys. Chem., B 1939, 43, 364.
13. Elam E. V., Davis H. W.: J. Org. Chem. 1967, 32, 1562.
14. Ugi I., Perlinger H., Behringer L.: Chem. Ber. 1958, 91, 2330.
15. Mukaiyama T., Tokizawa M., Nohira H., Takei H.: J. Org. Chem. 1961, 26, 4381.
16. Klingsberg E.: Synthesis 1972, 475.
17. Patel M. R., Mankad B. N.: J. Indian Chem. Soc. 1964, 41, 841.
18. Neber P. W., Burgard A., Thier W.: Justus Liebigs Ann. Chem. 1936, 526, 277.
Collect. Czech. Chem. Commun. 2010, Vol. 75, No. 8, pp. 871–885